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R Brödemann

Publications and source records attributed to R Brödemann.

15 recordsLinked to original sources

Simultaneous activation and opioid modulation of long-term potentiation in the dentate gyrus and the hippocampal CA3 region after stimulation of the perforant pathway in freely moving rats.

Recent investigations indicate monosynaptic activation by the perforant pathway (pp) of the dentate gyrus and the CA3 region. While short-term potentiation and long-term potentiation (LTP) and its opioid modulation are frequently described for the dentate gyrus, data for the CA3 region are rare. Therefore, evoked potentials and opioid modulation of LTP were directly compared in both target regions of the pp. Male Wistar rats were chronically implanted with a bipolar stimulation electrode in the pp (angular bundle) and two recording electrodes in the dorsal dentate gyrus and the CA3 region. Stimulation of the pp in the freely behaving animals induced short-latency evoked potentials in both target structures which were compared with respect to waveform, latency, amplitude and signs of short- and long-term neuronal plasticity. The short-latency potential in the CA3 region seemed to be a monosynaptic potential which displayed LTP sensitive to the N-methyl-D-aspartate receptor antagonist, MK 801, and depotentiating stimulation. After application of specific opioid antagonists at the mu-, delta- and kappa-opioid receptor subtypes, naloxone, funaltrexamine, naltrindole and binaltorphimine, different effects on induction and maintenance of LTP of the population spike were found both within the dentate gyrus and between the dentate gyrus and the CA3 region. The results show marked diminution of LTP in the dentate gyrus only for naloxone and naltrindole and only small, if any, effects of naloxone on LTP in the CA3 region. Thus, neuronal plasticity in the direct perforant pathway input to the CA3 region seems not to be under such substantial opioidergic control. LTP would be inducible in that region even when LTP in the input formation, the dentate gyrus, and transsynaptic LTP via the mossy fibres are blocked.

Animals↗

Activation of the dentate gyrus by stimulation of the contralateral perforant pathway: evoked potentials and long-term potentiation after ipsi- and contralateral induction.

Rats were chronically implanted with stimulation electrodes in the perforant pathway (pp) bilaterally and a recording electrode in the dentate gyrus (DG) unilaterally. Evoked field potentials (EPs) were recorded upon alternating stimulation of the pp on both sides, and long-term potentiation (LTP) was induced. Besides the EP after ipsilateral stimulation, an EP with a latency of approximately 5.5-6.5 ms was also seen upon stimulation of the contralateral pp. This potential was reversibly abolished during pentobarbital anesthesia and irreversibly after lesioning of the ipsilateral angular bundle. Paired-pulse facilitation and paired-pulse depression, depending on interstimulus interval and intensity, were also observed. Therefore, this long-latency potential could be characterized as polysynaptic and induced perhaps by transsynaptic activation via the ipsilateral entorhinal cortex. Ipsilateral tetanization induced strong E/S potentiation of both the ipsilaterally and contralaterally evoked EP, but with different time courses. Tetanization of the contralateral pp did not induce LTP of the ipsilaterally induced EP in the first 4 h. But afterwards a late and slowly developing potentiation occurred. The contralaterally induced EP also showed potentiation of the population spike, which was not immediately detectable but developed slowly over time. The results can be interpreted such that, after stimulation of the pp, the DG on the opposite side cannot only be activated via the weak crossed entorhinal projection but also transsynaptically via an entorhino/entorhinal connection.

Animals↗

Morphine self-administration in mu-opioid receptor-deficient mice.

Morphine-induced place preference was demonstrated recently in wild-type mice, whereas this conditioned behaviour was not observed in mu-opioid receptor-deficient mice. In the present study, we investigated locomotor effects of subcutaneously (s.c.) injected morphine as well as intracerebroventricular (i.c.v.) morphine self-administration in mu-opioid receptor-knockout mice. After s.c. morphine injection, locomotor activity significantly increased in wild-type animals. As expected, in the self-administration test the rate of self-administration constantly increased in wild-type mice reflecting reward effects of morphine. This increase was independent of locomotor/motor activity. In contrast, self-administration rates and locomotor/motor activity significantly decreased in the receptor-deficient animals. It was shown that this aversive effect might partly be due to kappa-opioid receptor interaction.

Analysis of Variance↗

Repeated long-term potentiation induces mossy fibre sprouting and changes the sensibility of hippocampal granule cells to subconvulsive doses of pentylenetetrazol.

Electrical and chemical kindling induces sprouting of the mossy fibre system and potentiation of evoked field potentials in the dentate gyrus. It has been postulated that such changes may also be induced by repeated induction of long-term potentiation (LTP) with tetanic stimulation of the perforant pathway. LTP was induced in rats chronically implanted with stimulation electrodes in the ipsilateral and contralateral angular bundles and with a recording electrode in the ipsilateral dorsal dentate gyrus. The animals were stimulated 10 times on 10 consecutive days but with different tetanization strengths. Sprouting of the mossy fibres terminating in the CA3 region was significantly induced only in the group of 'strongly' tetanized animals, but not in that of 'weakly' tetanized animals, or in low-frequency stimulated animals. Additionally, a novel form of potentiation which was previously found in pentylenetetrazol (PTZ)-kindled animals was also observed in the group of 'strongly' and 'weakly' tetanized rats. Differences in duration of this potentiation were found between the two groups of animals tetanized with different strengths. The results further demonstrate that morphological and functional changes in the hippocampus, similar to those seen after kindling, can also occur in an activation paradigm leading to long-lasting synaptic plasticity but not accompanied by seizure activity.

Action Potentials↗

Non-opioid antitussives and methadone differentially influence hippocampal long-term potentiation in freely moving rats.

Long-term potentiation (LTP) of monosynaptically evoked field potentials (MEFP) in the dentate gyrus of freely moving rats following tetanization of the perforant pathway was investigated after peripheral application of substances which have been shown to influence NMDA receptor-mediated effects (dextromethorphan, methadone) as well as structurally related substances with similar antitussive effects (codeine, normethadone). The noncompetitive NMDA receptor antagonist MK 801 was also tested for comparison. Whereas under control conditions the field e.p.s.p. (excitatory postsynaptic potential) and the population spike of the MEFP were largely uninfluenced by these substances, different effects were seen after the induction of LTP. MK 801 (0.2 mg/kg i.p.) suppressed the induction of LTP of both the field e.p.s.p. and the population spike. Dextromethorphan (40 mg/kg i.p.) also prevented the potentiation of the field e.p.s.p. and the population spike, thus resembling MK 801 in its effect. Codeine (20 mg/kg i.p.), the levorotatory structural analogue of dextromethorphan had no effect. Methadone and normethadone did not influence the potentiation of the field e.p.s.p. or interfere with the induction of potentiation of the population spike but depressed its maintenance. The results obtained with MK 801 confirm those reported by others. Comparison of the effects of dextromethorphan with those of MK 801, suggests that there is a direct interaction with the NMDA receptor-ionophore complex. The effects of methadone and normethadone appear not to be linked to an interaction with opioid receptors, since naloxone did not influence the suppression of LTP caused by methadone. The possibility of interference with the NMDA receptor-ionophore complex is discussed.

Animals↗

Long-term potentiation induced in dendrites separated from rat's CA1 pyramidal somata does not establish a late phase.

In 14 transversal hippocampal slices from rats the extracellular field-EPSP (excitatory postsynaptic potential) in the dendritic region of the CA1 subfield was recorded after isolating the apical dendrites from their somata by microsurgical cuts through the proximal stratum radiatum. Contrary to intact slices which, after tetanic stimulation of the Schaffer collaterals, showed long-term potentiation (LTP) until the end of registration after 8-10 h, LTP declined in the isolated dendrites to baseline values after 3 h. It is concluded that de-novo protein synthesis in postsynaptic cell bodies might be necessary for the maintenance of late phases of LTP.

Action Potentials↗

Habituation of monosynaptic field potentials in the dentate gyrus of freely moving rats interferes with LTP.

In 30 male Wistar rats, monosynaptically evoked field potentials in the dentate gyrus were registered under different conditions of repetitive stimulation and the long-term changes in synaptic transmission studied. Low-frequency stimulation induces a habituation-like decrement of the field-EPSP, but not of the population spike which interferes with the maintenance of LTP when administered after tetanic stimulation. The habituation-like response decrement, however, does not influence paired pulse-depression seen with an interstimulus interval of 20.0 ms. The paired pulse-plasticity, on the other hand, can be influenced by the tetanic stimulation (diminution of facilitation or depression), being dependent on the intensity of test stimuli. The results can be interpreted in terms of a complex influence of low-frequency- and tetanic stimulation on the elements of the dentate local circuitry and point to the necessity of considering long-term plastic changes in the investigation of substance- or stimulation-induced deviations of neuronal responses.

Action Potentials↗

Inhibitors of calmodulin and protein kinase C block different phases of hippocampal long-term potentiation.

The effects of a calmodulin (CaM) inhibitor, which does not influence Ca2+ fluxes (calmidazolium, RO-24571), and a new potent inhibitor of protein kinase C (K-252b) on long-term potentiation (LTP) were compared in hippocampal slices. Tetanic stimulation of the stratum radiatum during perfusion of calmidazolium (50 nM) failed to induce the characteristic post-tetanic and long-term increase in the magnitude of CA1-evoked responses. During perfusion with K-252b (50 nM) post-tetanic potentiation and initial LTP is expressed normally, but thereafter declines back to baseline with a 60 min delay. By themselves, the inhibitors had no significant effect on synaptic transmission in a non-tetanized control input. Our data are in line with current evidence from several laboratories that CaM- and protein kinase C (PKC)-dependent processes are involved in LTP and support the hypothesis that CaM mediates initiation and that PKC mediates mechanisms underlying the maintenance of LTP.

Action Potentials↗

The duration of long-term potentiation in the CA1 region of the hippocampal slice preparation.

The duration of long-term potentiation (LTP) of the monosynaptic excitatory Schaffer collateral-commissural input to hippocampal neurons of the CA1 region was examined in the in vitro slice. Relatively stable evoked potentials were obtained under conventional perfusion conditions at least for 10 hours. Tetanic stimulation (100 Hz, 1 sec) increased the population spike (pop-spike) amplitude by about 150% and the slope of the field-EPSP by about 30% over the pre-LTP baseline, whereas the latency and peak latency of the pop-spike decreased. In comparison to control experiments (same number of stimuli at 0.2 Hz) the differences were statistically significant for 2 hr (field-EPSP) and for greater than or equal to 10 hr (pop-spike), respectively. Repeated tetanization (3 X 100 Hz/1 sec), however, substantially prolongs EPSP-LTP (greater than or equal to 10 hr) and doubles the approximated half-life of pop-spike LTP. The threshold current intensity to elicit pop-spike responses decreased after the induction of LTP. Furthermore, the smaller field-EPSP values necessary to evoke near-threshold pop-spikes demonstrate an E-S potentiation (left-shift) at least in the low-intensity range. While the total duration of potentiation of the different parameters has not been determined, all the above mentioned effects could be observed at least 10 hr following the repeated tetanization. It is proposed that the slice preparation is suitable for the investigation of mechanisms of a postulated late phase of LTP if appropriate conditions are used.

Animals↗

PAGE-autoradiography of fucose incorporation into rat hippocampal glycoproteins after acquisition of a brightness discrimination.

Male rats aged 8 weeks received intraventricular injections of 100 microCi (3.7 MBq) L-[1-3H] fucose each, 7 h after acquisition of a brightness discrimination task. Two, 8 and 24 h as well as 16, 29 and 60 days after injection of labelled fucose hippocampal tissue was prepared to obtain Tris-soluble, Triton-soluble and Triton-resistant fractions. Two and 8 h after application of [3H]fucose, the trained animals revealed an increased incorporation of fucose mainly into the Triton-soluble glycoproteins. However, it is considered that also material from the Tris-soluble fraction may be used as an additional precursor for Triton-soluble glycoproteins. Quantitative analysis of autoradiographic densitograms obtained after SDS-polyacrylamide gel electrophoresis showed the occurrence of a training-related increase in fucose incorporation predominantly into the slow-moving Triton-soluble glycoproteins. The latter exhibited a higher turnover rate than the faster-moving glycoproteins. For the longer incorporation times (days) after injection of labelled fucose, no differences were observed between trained animals and corresponding active and passive controls.

Animals↗

Identical responses of the two hippocampal theta generators to physiological and pharmacological activation.

The possible existence of two separate RSA generators in the dorsal hippocampus raises questions as to the degree of coupling or independence of both. In order to answer these questions bipolar EEG recording were made in the CA1 and dentate gyrus of freely moving rats during conditions of RSA generation by different manipulations. The quantitative EEG parameters of simultaneous records were compared and cross correlation functions were calculated. Results indicate that even under different conditions of inducing RSA (physiological activation or injection of arecoline and nicotine) yielding RSA with different frequency characteristics, the quantitative EEG parameters were similar in both recordings. In addition, a high degree of concordance of both EEG was evidenced in the cross correlation function. These observations are discussed in terms of a high degree of coupling between both RS generators.

Animals↗